|
|
Abstract
Lower scores of nelfinavir metabolite M8 were associated with virological failure at 24 weeks of early antiretroviral therapy in primary HIV-1 vertically infected children in the Penta 7 study
Compagnucci A.1, Saïdi Y.1, Gibb D.M.2, Rampon O.3, Ramos Amador J.4, Feiterna Sperling C.5, Reliquet V.6, Giaquinto C.3, Girard S.1, Harper L.2, Burger D.7, Treluyer J.8, Jacqz-Aigrain E.9, Faye A.10
Background: Early treatment with d4T+ddI+NFV administered to 20 HIV-1 infected infants (<=3 months) was associated with incomplete viral suppression (<400 cp/mL) in 70% of infants even with high doses of NFV (150 mg/kg/day).
Objectives: To investigate the relationship between virologic response and NFV and its metabolite M8.
Methods: Percentiles values of NFV and M8 for times H0, H1, H2, H4, H6, H8 and H12 were calculated from 3 PK studies performed in PENTA 7 at 3, 6 and 18 months of age. In addition, trough levels (TL) of NFV and M8 from plasma samples taken through 72 weeks of follow-up were analysed. Each TL was reported as ‘acceptable’ if it was above its respective 25th percentile value considered as the minimal target value. Thus for each infant, a score was calculated as the proportion of the number of ‘acceptable’ TL to the total number of TL. Scores were compared between responders and non-responders after 24 weeks and 48 weeks.
Results: 139 TL of NFV and M8 were analysed. NFV was lower in children under 6 months vs > 6 months whereas this trend was not observed for M8. Percentiles values were calculated for each time point from 27 PK studies in 14 infants. Scores of NFV in 9 responders and 11 non responders at week 24 were 0.71 and 0.54 respectively (P=0.23), with the same trend at week 48. However for M8, scores at week 24 were significantly different (0.80 vs 0.52; P=0.025). This trend in M8 was still observed in 6 responders and 14 non-responders at week 48 although with a non significant difference (0.78 vs 0.59; P=0.15).
Conclusions: In infants treated during HIV-1 primary infection, metabolite M8 appears to be associated with virologic failure at 24 weeks. Specificity of metabolism in infants may explain this finding.
The 3rd IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
MoPe9.2C15
Suggested Citation
"CompagnucciA., et al.
Lower scores of nelfinavir metabolite M8 were associated with virological failure at 24 weeks of early antiretroviral therapy in primary HIV-1 vertically infected children in the Penta 7 study.
Poster Exhibition:
The 3rd IAS Conference on HIV Pathogenesis and Treatment:
Abstract no.
MoPe9.2C15"
|
|
|